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UNTIL 12:01 AM EST
Thursday,
September 25, 2008
Contact: Donna Krupa
Office: (301) 634-7209
Newsroom Phone: 843-681-0794 or 95
Cell: 703-967-2751
dkrupa@the-aps.org
Cholesterol-Lowering Drugs
And The Effect On Muscle Repair And Regeneration
Primary
human cell study finds simvastatin at high doses may have a negative impact
on the body’s muscles
HILTON HEAD, SC—Statins are powerful drugs that reduce “bad”
cholesterol and thus cut the risk of a heart attack. While these medications
offer tremendous benefits to millions, they can carry side effects for some.
The most frequently reported consequence is fatigue, and about nine percent
of patients report statin-related pain. Both can be exacerbated when statin
doses are increased, or physical activity is added. The results of a new
study may offer another note of caution for high-dose statin patients.
Working with primary human satellite cell cultures, researchers have found
that statins at higher doses may affect the ability of the skeletal
muscles–which allow the body to move–to repair and regenerate themselves.
The study is entitled “Simvastatin Reduces Human
Primary Satellite Cell Proliferation in Culture.” It was conducted by Anna
Thalacker-Mercer, Melissa Baker, Chris Calderon and Marcas Bamman,
University of Alabama at Birmingham. They will discuss their findings at the
American Physiological Society (APS; (www.The-APS.org)
conference, The Integrative Biology of Exercise V. The meeting
is being held September 24-27, 2008 in Hilton Head, SC.
“Watch the researcher
discuss her work.”
The Study
Statins have been reported to have adverse effects on
skeletal muscle in both human and animal models causing cramping and fatigue
and potentially myopathy. Relatively little is known regarding the effect
of statins on the muscle progenitor cells (i.e., satellite cells (SC)) which
play a key role in skeletal muscle repair and regeneration following
exercise or injury. SC remain in a quiescent state until stimulated to
proliferate. Statins are known to have antiproliferative effects in other
cell types and therefore may inhibit or effect this critical step in muscle
repair. Thus it is important to understand the influence of statins on SC
function which may further affect the overall health and physiology of human
skeletal muscle..
The study examined the proliferative capacity of human
satellite cells in culture, which were exposed, to a lipophilic statin:
simvastatin. The aim of the study was to determine SC viability during
proliferation when treated with statins which may be indicative of the
ability of SCs to undergo mitosis (i.e. divide to make new cells).
The research team used primary cell lines isolated from
quadriceps muscle biopsies. SC were mixed and grown for 48 hours with
several concentrations of statin: 0.0, 0 plus the solvent DMSO (control),
0.05, 0.1, 1.0, 10, or 100µM. The MTS assay was utilized to measure cell
viability/reproducibility.
Additionally the investigators determined the effects
of varying concentrations of simvastatin on SCs in different states (i.e.,
undergoing differentiation or differentiated into myotubes).
Key Findings
The researchers found the following:
There was a dose dependent decrease in the viability of the
satellite cells at 1.0, 10 and 100µM concentrations of simvastatin. At
approximately 5.0 µM concentration the viability of the proliferating cells
was reduced by 50% (equivalent to the availability of simvastatin in
circulation from a 40 milligram dose per day used in some patients).
Specifically, the higher end concentrations led to reduced SC proliferation,
which would likely negatively affect the muscle’s ability to heal and/or
repair itself.
There was no change in the viability of satellite cells at
concentrations of 0.05 or 0.1µM.
Cell viability was reduced by approximately half in
differentiating cells and myotubes with concentrations of 1.0 and 5.0 µM,
respectively.
Next Steps
According to Dr. Thalacker-Mercer, a member of the
research team, “While these are preliminary data and more research is
necessary, the results indicate serious adverse effects of statins that may
alter the ability of skeletal muscle to repair and regenerate due to the
anti-proliferative effects of statins.”
Looking ahead, she added, “We are very interested in
these effects in the older population. It is possible that older adults may
not be able to distinguish between muscle pain related to a statin effect or
an effect of aging and therefore adverse effects of statins in older adults
may be under-reported. Therefore, our next step is to examine statins among
older adults.”
*****
Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease. The American Physiological Society (APS;
www.The-APS.org/press) has been an integral part of this discovery
process since it was established in 1887.
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NOTE TO EDITORS: The
APS Conference, The Integrative Biology of Exercise V, is being held
September 24-27, 2008 in Hilton Head, SC. Members of the media are invited
to attend. To register, or to schedule an interview with Drs. Bamman or
Thalacker-Mercer, please contact Donna Krupa at 301.634.7209 (office),
703.967.2751 (cell) or
DKrupa@the-APS.org. There will be an APS newsroom onsite.
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